UW team builds artificial enzyme

UW Chemistry professors Michael Gelb and Forrest Michael, in collaboration with Prof. David Baker (UW Biochemistry), have engineered an artificial enzyme capable of catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. Their findings were reported July 16 in Science. The team of collaborators used computer modeling to screen over 10 billion possible protein backbone geometries for the ones that could support the right combination of active sites and catalytic residues. From this list, and further optimization, 84 de novo designs were selected for experimental work. Ultimately, two of the designed enzymes showed the ability to catalyze the Diels-Alder reaction.

The Diels-Alder reaction is one of the cornerstones of synthetic chemistry and no naturally occurring enzymes have been shown to catalyze it. Broader application of de novo enzyme design should be significantly useful in synthetic chemistry.